title: Phase II trial of paclitaxel, carboplatin and gemcitabine in patients with locally advanced carcinoma of the bladder.
abstract: OBJECTIVE
  This 2-arm phase II multicenter trial was designed to assess the efficacy and toxicity of neoadjuvant paclitaxel, gemcitabine and carboplatin in patients with invasive bladder cancer.
  
  
  METHODS
  Patients in arm I had clinical stage T2 with hydronephrosis or T3 bladder cancer. They received 3 cycles of chemotherapy (200 mg/m(2) paclitaxel on day 1, AUC 5 carboplatin on day 1, and 800 mg/m(2) gemcitabine on days 1 and 8 of each 21-day cycle). Response was defined as achievement of a pathological complete response (pT0). Patients in arm II with T4 or lymph node positive disease received up to 6 cycles of paclitaxel, carboplatin and gemcitabine. Response was defined as conversion to surgical resectability.
  
  
  RESULTS
  In arm I, 31 patients were enrolled and 22 were evaluable for response. Seven patients had pT0 disease (32% of evaluable patients, 22% by intent to treat). In arm II, 37 patients were enrolled and 29 were evaluable for response with 24 suitable for surgical resection (83% of evaluable and 65% by intent to treat). The most common toxicity was neutropenia with 39 events in arm I and 68 in arm II. There were 7 deaths on study (5 during chemotherapy and 2 after cystectomy).
  
  
  CONCLUSIONS
  Neoadjuvant paclitaxel, carboplatin and gemcitabine resulted in a significant number of responses in both arms but greater than anticipated toxicity. The pT0 rate was modest and overall efficacy was difficult to assess due to the toxicity. More studies of novel agents and combinations are needed to improve the efficacy and reduce the toxicity of neoadjuvant therapy for bladder cancer.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan School of Medicine, University of Michigan, Ann Arbor, Michigan, USA. dcsmith@umich.edu
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.forename: Niklas J
authors.initials: NJ
authors.lastname: Mackler
authors.forename: Rodney L
authors.initials: RL
authors.lastname: Dunn
authors.forename: Maha
authors.initials: M
authors.lastname: Hussain
authors.forename: David
authors.initials: D
authors.lastname: Wood
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.forename: Martin
authors.initials: M
authors.lastname: Sanda
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Kathleen
authors.initials: K
authors.lastname: Beekman
authors.forename: James E
authors.initials: JE
authors.lastname: Montie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D000093542:Gemcitabine